Spray drying encapsulation of CD-MOF nanocrystals into Eudragit® RS microspheres for sustained drug delivery

Abstract

Sustained release microspheres containing γ-cyclodextrin metal-organic frameworks (CD-MOF) was designed to improve oral bioavailability and control the release of indomethacin (IMC). The CD-MOF nanocrystals were encapsulated with Eudragit® RS by spray drying technology to regulate the release rate of indomethacin. The morphology, physical states and pore structure of the CD-MOF nanocrystals and CD-MOF@Eudragit® RS microspheres were investigated by scanning electron microscopy, X-ray diffraction, and nitrogen adsorption. Fourier infrared transform spectroscopy revealed the presence of intermolecular interactions between the CD-MOF and indomethacin. Drug-loaded CD-MOF nanocrystals exhibited significantly higher dissolution rate compared with raw IMC during the in vitro release studies. And the encapsulation of CD-MOF nanocrystals with Eudragit® RS significantly reduced the initial burst release of the loaded drug. Pharmacokinetic studies in SD rats showed both IMC/CD-MOF nanocrystals and IMC/CD-MOF@Eudragit® RS microspheres increased oral bioavailability of IMC compared with raw IMC. Meanwhile, the IMC/CD-MOF@Eudragit® RS microspheres achieved a significantly prolonged Tmax value than the raw IMC and IMC/CD-MOF nanocrystals, indicating sustained release of the loaded drug. The strategy of spray drying composite microspheres of CD-MOF nanocrystals and organic polymer for sustained drug release can be applied to the design of oral drug delivery systems of other poorly soluble drugs.